Method for preventing the crystallisation of pharmaceuticals in a polymer film

Abstract

The invention relates to a method for preventing the crystallization of a pharmaceutical in a polymer film, wherein the solvent-containing coating compound, which comprises a matrix-forming polymer or polymer mixture and at least one pharmaceutical and is spread to produce the polymer film, is temporarily dried at temperatures that is at least 10° C. above the melting temperature of the pharmaceutical contained in the coating compound. The maximum temperature is thus higher than that which is required for mere drying and obviates the need for an additional, time-consuming and expensive work step.

The invention claimed is: 
     
       1. A method for preventing the crystallization of a pharmaceutical in a polymer film, comprising
 applying a solvent-containing coating material onto a substrate to produce a polymer film, said coating material further comprising a matrix-forming polymer or polymer mixture and at least one pharmaceutical present in dissolved form and having a melting temperature, 
 drying the coating material at temperatures which are at times 10 to 25° C. above the melting temperature of the pharmaceutical present in the coating material, 
 wherein said drying step further comprises drying the coated material for not longer than 15 minutes at temperatures which are 10 to 25° C. above the melting point of the pharmaceutical, 
 and the drying temperature does not exceed 130° C. 
 
     
     
       2. The method of  claim 1 , wherein the temperatures are at times 15 to 25° C. above the melting temperature of the pharmaceutical. 
     
     
       3. The method of  claim 1 , wherein the coated material is dried for at least 1 minute at temperatures which are 10 to 25° C. above the melting point of the pharmaceutical. 
     
     
       4. The method as claimed in  claim 3 , wherein the coated material is dried for at least 100 seconds. 
     
     
       5. The method as claimed in  claim 3 , wherein the coated material is dried for at least 3 minutes. 
     
     
       6. The method of  claim 1 , wherein the matrix-forming polymer or at least one of the polymers of the matrix-forming polymer mixture is selected from the group consisting of polysiloxanes, polyacrylates, polyisobutylenes, and block copolymers. 
     
     
       7. The method of  claim 1 , wherein the matrix-forming polymer is an amine-resistant polysiloxane. 
     
     
       8. The method of  claim 1 , wherein the solvent is selected from the group of organic solvents consisting of heptane, hexane, cyclohexane, ethyl acetate, ethanol, methanol, isopropanol, and tetrahydrofuran. 
     
     
       9. The method of  claim 1 , wherein the pharmaceutical has a melting temperature of below 120° C. 
     
     
       10. The method as claimed in  claim 9 , wherein the pharmaceutical has a melting temperature of below 115° C. 
     
     
       11. The method as claimed in  claim 9 , wherein the pharmaceutical has a melting temperature of below 105° C. 
     
     
       12. The method of  claim 1 , wherein the pharmaceutical is selected from the group consisting of rotigotine and fentanyl. 
     
     
       13. The method as claimed in  claim 1 , wherein the coated material is dried for not longer than 10 minutes. 
     
     
       14. The method as claimed in  claim 1 , wherein the coated material is dried for not longer than 5 minutes. 
     
     
       15. A method for preventing the crystallization of a pharmaceutical in a polymer film, comprising
 applying a solvent-containing coating material onto a substrate to produce a polymer film, said coating material further comprising a matrix-forming polymer or polymer mixture and at least one pharmaceutical present in dissolved form and having a melting temperature, 
 drying the coating material at temperatures which are at times 10 to 25° C. above the melting temperature of the pharmaceutical present in the coating material, 
 
       wherein said drying step further comprises drying the coated material for not longer than 15 minutes at temperatures which are 10 to 25° C. above the melting point of the pharmaceutical, said pharmaceutical is rotigotine and said method further comprises forming a two-phase polymer mixture. 
     
     
       16. A method for preventing the crystallization of a pharmaceutical in a polymer film consisting of
 applying a solvent-containing coating material onto a substrate to produce a polymer film, said coating material further comprising a matrix-forming polymer or polymer mixture and at least one pharmaceutical present in dissolved form, 
 drying the coating material in one continuous operation at temperatures which are at times 10 to 25° C. above the melting temperature of the pharmaceutical present in the coating material, 
 wherein said drying step further comprises drying the coated material for not longer than 15 minutes at the temperatures which are 10 to 25° C. above the melting point of the pharmaceutical, and 
 the drying temperature does not exceed 130° C. 
 
     
     
       17. The method of  claim 16 , wherein the polymer film is within a transdermal therapeutic system further comprising a backing layer and a protective layer. 
     
     
       18. The method of  claim 16 , wherein said method further comprises administering said polymer film orally.